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BDS1 BAMS: Pathology > Adaptive Immunity 1 + 2 > Flashcards

Adaptive Immunity 1 + 2 Flashcards

1
Q

What does “humoral” mean

A

Anything produced by cells e.g. antibodies

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2
Q

What 2 groups of responses does adaptive immunity consist of?

A

Cell-mediated responses and antibody (humoral) responses

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3
Q

Which cells drive cell-mediated immunity the adaptive response?

A

T cells

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4
Q

Which cells drive humoral immunity in the adaptive response?

A

B cells

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5
Q

What does “immunological memory” refer to?

A

Each pathogen is “remembered” by a signature T cell and/or B cell receptor

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6
Q

Describe the kinetics of adaptive immunity

A

Arises following innate immunity. Usually 4-7 days following infection.

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7
Q

What are the stages in adaptive immunity?

A
  1. Infection
  2. Transport of antigen to lymphoid organs
  3. Recognition by naive B and T cells
  4. Clonal expansion and differentiation to effector cells
  5. Removal of infectious agent
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8
Q

What are the 3 main receptors in adaptive immunity?

A

T cell receptor (TCR)
B cell receptor (immnunoglobulins - Ig)
Major histocompatibility complex (MHC proteins)

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9
Q

What is the difference between innate and adaptive receptors?

A 
Innate receptors e.g. TLRs do not have the potential to rearrange and change shape to recognise different antigens
Adaptive receptors (TCR, Ig, MHC) can rearrange their structure depending on gene expression of each protein subunit
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10
Q

Where do T cells originate?

A

Bone marrow

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11
Q

Where do T cells mature?

A

Thymus

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12
Q

What does the T cell repertoire refer to?

A

The diversity in T cell receptors - can respond to numerous antigens

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13
Q

What is the purpose of ‘thymus eduction’?

A

Ensures T cells only respond to foreign pathogens and not ‘self peptides’

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14
Q

What is the role of T helper cells (CD4+)?

A

Help support other immune cells fight threats

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15
Q

What is the role of cytotoxic T cells (CD8+)?

A

Destroy our own cells which have become infected (usually virus-related)

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16
Q

What is the role of regulatory T cells (Tregs)?

A

Regulate or suppress other cells in the immune system

Balance homeostasis between pro and anti inflammatory responses

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17
Q

What is the role of the CD8 receptor (in CD8+ T cells)?

A

CD8 is a co-receptor that binds to MHC I

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18
Q

What is the role of the CD4 receptor (in CD4+ T cells)?

A

CD4 is a co-receptor that binds to MHC II

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19
Q

What is the role of the CD3 receptor?

A

CD3 is a co-receptor involved in activation of both CD4+ and CD8+ T cells

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20
Q

What are the 2 classes of T cell receptor?

A

Alpha and beta chains (CD4+, CD8+)

A small proportion express gamma and delta chains instead (CD4-, CD8-)

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21
Q

What is VDJ recombination?

A

Multiple genes code for each of the 2 chains of T Cell receptors (alpha chain and beta chain)

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22
Q

What are the 2 regions in the chains of the T cell receptor?

A

Constant region - does not change in structure

Variable region - protrudes from the membrane, helps receptor bind to antigen

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23
Q

What are the 3 gene segments that encode the variable regions in the chains of T cell receptors?

A

V (variable) - both alpha and beta chains
D (diversity) - beta chain only
J (joining) - both alpha and beta chains

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24
Q

What is the name of the process that results in gene re-arrangement, and which enzymes drive the process?

A

Somatic recombination

RAG (recombinase) enzymes

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25
Q

What does somatic recombination lead to in T cell receptors?

A

Different receptor structures that can recognise different antigens i.e. different antigen binding sites

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26
Q

How many different combinations of receptors are possible in T cell receptor VDJ recombination?

A

100 billion

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27
Q

What happens during thymic education?

A

Pre-thymic T cells enter the thymus
T cells interact with cortical epithelial cells in the thymus
There are 2 types of selection: positive selection and negative selection
Positive selection - no recognition = apoptosis
Negative selection - recognition of self-antigen = apoptosis

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28
Q

Describe the process of T cell emigration

A

Positively and negatively selected CD4/CD8+ T cells with rearranged T cell receptors leave the thymus and circulate in the blood/lymphatics
Some reside in lymph nodes
These T cells are educated but still ‘naive’ until they interact with AP cells

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29
Q

Describe T cell activation by dendritic cells

A

Immature dendritic cells take up an process antigen in the epidermis
Once DCs have taken up antigen, they migrate to lymph nodes and mature en route
Mature DCs have co-stimulatory activity and can prime naive T cells

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30
Q

Describe the process of ‘priming’ naive T cells

A

3 signals are required for activation and determining the fate of T cells:

  1. MHC-TCR interaction
  2. Co-stimulatory molecules interaction (CD80/CD86 and CD40 on DC; CD40L and CD28 on T cell)
  3. Cytokines - this signal dictates what T helper cell the naive T cell will become
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31
Q

What are the 3 signals required for activation and determining the fate of T cells?

A
  1. MHC-TCR interaction: activation of T cells
  2. Co-stimulatory molecules interaction (CD80/CD86 and CD40 on DC; CD40L and CD28 on T cell): survival and clonal expansion of T cells
  3. Cytokines: differentiation into subsets of effector T cells
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32
Q

What does the 3rd signal during priming result in in CD8+ T cells?

A

Effector function e.g. production of enzymes for degradation

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33
Q

In priming, signal one without signal 2 is known as what?

A

Anergy

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34
Q

What are the subsets of CD4+ helper T cells?

A

TH1 = macrophage
TH2 = allergic repsonses/plasma cell generation
TH17= epithelium and underlying tissue cell types
TFH = important for B cell antibody generation
Treg cells = control/dampen the immune response

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35
Q

Interferon-gamma is produced by TH1 cells. What is the purpose of interferon-gamma?

A

Instructs immune cells such as macrophages and cytotoxic T cells to destroy infected cells

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36
Q

What is the role of TH2 cells?

A

Support humoral responses and allergic reactions. Source of interleukin 4,5 and 6 (IL-4, IL-5 and IL-6), which instruct B cells to produce antibodies

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37
Q

What is the role of TH17 cells?

A

Supporting innate immune responses
Enhances clearance of extracellular bacteria and fungi
Produces IL-17 and IL-22

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38
Q

What is the role of TFH cells?

A

T follicular helper cells are found in secondary lymphoid organs
Work with B cells for antibody production

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39
Q

What is the role of TH1 cells?

A

Main role in supporting macrophage function

Source of interferon-gamma

40
Q

What is the purpose of Treg cells?

A

Function in immune suppression
Release inhibitory cytokines (IL-10)
Inhibit T cell activation and DC activation

41
Q

What is the role of CD8+ cells?

A

Activation arises from interaction between MHCI and TCR
Induce host cells to undergo apoptosis
Produces enzymes such as granzyme and perforin
Perforin targets apoptotic signalling pathways

42
Q

What do perforins and granzymes do? (produced by CD8 cells)

A

Perforin form pores in the plasma membrane

Granzymes enter the cell and break down proteins, lysing the cell

43
Q

Where do B cells mature?

A

In the bone marrow

44
Q

Where are B cells found in large numbers

A

B cells circulate in the blood and the lymph and are found in large numbers in the lymphoid organs

45
Q

How do B cells recognise antigens?

A

Through the B cell receptor (BCR), which is the actual antibody (IgM or IgD)

46
Q

What does diversity in the BCR enable B cells to do?

A

Diversity in the BCR = potential to respond to numerous antigens

47
Q

What do B cells change into once activated?

A

Plasma cells - “antibody factories”

48
Q

What are the 5 types of immunoglobulins produced by B cells?

A

IgG, IgE, IgD, IgM, IgA

IgM and IgD are BCRs

49
Q

Which class of antibody is the first to be secreted after an antigen is encountered?

A

IgM

50
Q

Which class of antibody is found primarily in glandular secretions such as mucus, tears, saliva and semen?

A

IgA

51
Q

Which is the most prominent antibody in the human body?

A

IgG

52
Q

Which class of antibody is capable of binding multiple antigens?

A

IgM

53
Q

Describe the structure of the B cell receptor (BCR)

A

Variable and constant regions

Made up of light and heavy chains

54
Q

What are the 3 main functions for antibodies in the human body?

A
  1. Neutralisation
  2. Opsonisation
  3. Initiation of complement
55
Q

What is the primary goal of antibodies in the human body?

A

Primary goal is to prevent microbial activity and aid removal of threat from host

56
Q

What is ‘neutralisation’?

A

Coats the outside of the pathogen, prevents it from having an effect in human body

57
Q

What is ‘opsonisation’?

A

Coating the pathogen to induce phagocytosis
Antibody dependent cellular cytotoxicity arises from opsonisation
Mast cell degranulation (allergy)

58
Q

What does ADCC stand for?

A

Antibody-dependent cellular cytotoxicity

59
Q

Which complement pathway is initiated via antibodies?

A

Classical pathway

60
Q

Where do B cells originate?

A

In the bone marrow

Also mature in the bone marrow

61
Q

What are the developmental stages of B cells defined by?

A

Rearrangements of the immunoglobulin heavy and light chains

62
Q

Describe the process of VDJ recombination in generating BCR diversity

A

Heavy chain involves rearrangements of V, D and J genes (similar to beta chain in TCR)
Light chain involves rearrangements of V and J genes (similar to alpha chain in TCR)

63
Q

What is the main receptor expressed on immature B cells?

A

IgM

64
Q

Which receptors are expressed on the surface of mature B cells?

A

IgM and IgD

65
Q

Which process ensures that there is no reactivity against self antigens in B cells, and how does this differ from T cells?

A

B cells undergo negative selection in the bone marrow
Macrophages engulf and remove self-reacting B cells
T cells undergo negative AND positive selection

66
Q

Where does B cell activation occur?

A

Predominantly in the lymph nodes, but some naive B cells can be activated in the periphery

67
Q

What are the two types of B cell activation?

A
  1. Thymus dependent activation: antigens which require T cell help
  2. Thymus independent activation: antigens which do not require T cell help
68
Q

What does activation of B cells result in?

A

Generation of plasma cells

69
Q

What are plasma cells known as?

A

Antibody factories

70
Q

Describe thymus dependent activation

A

Antigens require T cell help
Co-receptor binding involves (CD40 on B cell to CD40L on T cell)
Cytokine signals released from T helper cell to induce proliferation
Generates pool of plasma cells
Generates memory B cells
Plasma cells initially produce IgM before undergoing class switching

71
Q

Describe thymus independent activation

A

Antigens do not require T cell help
Certain antigens e.g. bacterial LPS can activate B cells directly
Response is weaker than thymus dependent activation
Does not lead to generation of memory B cells - no long term immunity

72
Q

Describe the process of ‘class switching’ in B cells

A 
Activation leads to class switching 
IgM response = first response
IgM response is weak; cells class switch to IgG (or IgA or IgE) 
Occurs by gene rearrangement BUT antigen binding site remains the same
Repeated exposure to antigen causes affinity maturation
73
Q

What does ‘affinity maturation’ mean?

A

The antibody has increasing affinity for antigen (stronger response)

74
Q

Define ‘affinity’ in B cells

A

Strength of binding of single antibody to antigen

75
Q

Define ‘avidity’ in B cells

A

Ability of antibodies to form complexes

76
Q

Which antibodies have a high affinity but low avidity for their antigen targets?

A

IgG, IgA and IgE

77
Q

Which antibody has a high avidity but low affinity for their antigen targets?

A

IgM

78
Q

Which antibody is decavalent?

A

IgM -> high avidity for antigen targets

79
Q

Which antibody is involved in allergy?

A

IgE

80
Q

Which antibody has the highest opsonisation and neutralisation activities?

A

IgG

81
Q

Describe ‘cross talk’ between B and T cells

A

In lymphoid organs, cross talk between B and T cells leads to generation of both ‘arms’ of the immune response:

  • Humoral immunity
  • Cellular immunity
82
Q

What is somatic hypermutation?

A

The response of an immune cell to external stimuli from an antigen e.g. class switching in B cells

83
Q

Which cells are important in the process of vaccinations against a specific antigen?

A

B cells and T cells

84
Q

Which classes of B cells are important in generating an immune response?

A

In the primary immune response, IgM acts early
B cells undergo class switching
IgG response follows

85
Q

What do memory T and B cells enable in the immune response?

A

Enable a faster immune response upon subsequent exposure to the antigen

86
Q

Describe the basic principle of vaccination

A

Antigen exposure leads to immunological memory
IgM acts early in the primary immune response. B cells undergo class switching and IgG response follows
The presence of memory B and T cells means that upon subsequent exposure, the immune system can respond much faster
Presence of cells that are primed to produce a more effective (IgG rather than IgM) response immediately
Secondary much more rapid and specific due to presence of memory cells

87
Q

What is immunological tolerance?

A

A state of immune unresponsiveness to a particular antigen
2 main types:
1) Central tolerance - in the primary lymphoid organs (thymus and bone marrow)
2) Peripheral tolerance - occurs outwit the primary lymphoid organs

88
Q

Describe the basis for central tolerance in T cells

A

Tolerance occurs due to selection
Occurs in the thymus
2 types of selection for T cells: negative and positive selection
This process leads to elimination of >90% of T cells

89
Q

Describe the basis for central tolerance in B cells

A

Tolerance occurs due to selection
Negative selection occurs in B cells - B cells that bind strongly to self antigen are eliminated
For B cells, occurs in the bone marrow

90
Q

What can happen if tolerance mechanisms are dysfunctional?

A

Autoimmunity

Allergies

91
Q

Describe peripheral tolerance in T cells

A

Not all self reactive T cells are eliminated
Peripheral tolerance prevents activation of self-reactive T cells
Signal 1 but no signal 2 = anergy
Signal 1 and 2 but no signal 3 = deletion by apoptosis
Treg cells can also directly block activity by binding antigen

92
Q

Describe peripheral tolerance in T cells

A

Occurs in secondary lymphoid organs
Self reactive B cells require help from self reactive T cells
Since most self-reactive T cells are eliminated, self-reactive B cells do not receive T cell help and therefore become anergic

93
Q

What does ‘breach of tolerance’ mean?

A

Self reactive T cells and B cells are not eliminated through selection mechanisms, and are activated. These cells produce an immune response against self antigens or commensal organisms
Breach of tolerance drives many autoimmune diseases

94
Q

What does immunological tolerance ensure?

A

That the immune system does not attack self antigens

95
Q

What is the purpose of central and peripheral tolerance checkpoints?

A

Prevent autoimmunity

96
Q

What does breach of tolerance lead to?

A

Reactivity against self antigens

BDS1 BAMS: Pathology (11 decks)

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